Dialysis modality and nutritional status are associated with variability of inflammatory markers.

BACKGROUND: Inflammation is a common feature in dialysis patients and is associated with cardiovascular complications and poor outcome. Measuring the variability of inflammatory markers may help in understanding underlying factors triggering inflammation. Whether the inflammatory pattern in hemodialysis (HD) and peritoneal dialysis (PD) patients differs has scarcely been studied. Here we explored factors associated with the magnitude and variability of inflammation markers in HD and PD patients. METHODS: In two 3-month, prospective cohort studies comprising 228 prevalent HD and 80 prevalent PD patients, interleukin-6 (IL-6) and high-sensitivity C-reactive protein (CRP) were measured in blood samples drawn each month and every week, respectively. Information on comorbidity, protein-energy wasting (PEW) and medications was gathered at baseline, and information on symptoms potentially related to inflammation was gathered weekly. A mixed-effect model was used for multivariate analysis of factors linked to CRP and IL-6 variation. RESULTS: IL-6 and CRP levels were higher and showed higher variability in HD versus PD patients [median IL-6 8.3 (interquartile range, IQR, 5.3-14.5) versus 6.7 (IQR 4.2-10.0) pg/mL, P < 0.001 and median CRP 6.1 (IQR 2.5-14.0) versus 5.4 (IQR 1.6-9.0) mg/L, P < 0.001). PEW predicted increased inflammation variability after correcting for age, sex, dialysis vintage, modality and comorbidity. Increased comorbidity predicted IL-6, but not CRP, variability. CONCLUSIONS: Circulating concentrations as well as variability of IL-6 and CRP levels were higher in HD as compared with PD patients. In HD and PD patients, short-term variability of IL-6 and CRP levels associated strongly with PEW, while comorbidity was related to IL-6 but not to CRP variability.

Delta-He: a novel marker of inflammation predicting mortality and ESA response in peritoneal dialysis patients.

BACKGROUND: Inflammation impairs erythropoiesis, iron availability and is associated with a higher mortality risk in patients with end-stage renal disease. We studied the associations between Delta-He [the difference between the reticulocyte haemoglobin content (Ret-He) and erythrocyte haemoglobin content], a suggested marker of iron availability, and markers of inflammation, iron status, response to erythropoiesis-stimulating agents (ESAs) and mortality in prevalent peritoneal dialysis (PD) patients. METHODS: Eighty-two PD patients were followed weekly for 12 weeks with an additional follow-up of 36 months. Delta-He, Ret-He and high-sensitivity C-reactive protein (hs-CRP) were measured weekly and interleukin-6 (IL-6) and iron markers every fourth week. Mortality risk was assessed by Cox proportional hazards model adjusting for potential confounding factors. The relationships between ESA response, inflammatory markers, iron markers and Delta-He were evaluated in the PD patients. The relationship between Delta-He and iron markers was analysed in 87 healthy subjects. RESULTS: Delta-He correlated with IL-6 (rho = 0.48, P < 0.001), hs-CRP (rho = 0.36, P < 0.001) and ESA hyporesponsivess index (EHRI; rho = -0.44, P < 0.001) in the PD patients. Delta-He did not correlate with iron markers in PD patients nor in healthy subjects. The mean Delta-He levels were significantly different between the tertiles of EHRI (P < 0.01). Delta-He was associated with all-cause mortality risk in PD patients after adjusting for age, gender, hs-CRP, comorbidity and nutritional status [OR 0.70 (0.51-0.96), P < 0.05]. CONCLUSIONS: Delta-He independently predicts all-cause mortality in PD patients after adjusting for potential confounders and is a predictor of ESA response in PD patients.